Candidate: This is the candidate's first faculty position as Assistant Professor at Univ. of Texas, Houston. During fellowship she learned both clinical and basic research techniques under the mentorship of Dr. Timothy Garvey. This training resulted in publication of 3 original research articles (published in peer reviewed journals), 6 abstracts presented at scientific meetings, & 2 clinical articles. During her first year as faculty, the candidate has developed several independent research protocols, maintained collaborative efforts with Dr. Garvey, & found mentorshlp from Dr. Dennis Bier. This year, she has had 3 publications in peer-reviewed journals and an oral presentation at the American Diabetes Association annual meeting. Research: The submitted research for KO8 Award involves the study of glucose metabolism and insulin action in Cystic Fibrosis patients. This is a timely study due to recently developed therapies (such as gene therapy) which will prolong life. Diabetes Mellitus & malnutrition are expected to become the principal causes of morbidity & mortality. Using 3-step hyperinsulinemic euglycemic clamp, the P.I. will determine insulin sensitivity in three groups of CF patients: NGTCF, IGTCF & DMCF. Hepatic glucose output will be determined using the stable isotope 6,6-2H-glucose by a "labeled-GINF" method. Insulin action on protein; turnover will be determined using the stable isotope [1-13C]leucine. Indirect calorimetry at baseline and maximal glucose uptake during the clamp will allow determination of glucose oxidation, non-oxidative glucose metabolism and lipid oxidation. Resting energy expenditure will be determined using indirect calorimetry. Results of insulin sensitivity data will be correlated with clinical outcome scores, as well as, genotypic markers for common CF mutations. Environment: The Texas Medical Center is uniquely equipped with multiple institutions and research investigators to provide one of the best training environments for a young investigator. The CF clinic at Texas Children's Hospital is a nationally recognized center for the treatment of CF. The patients receive carefully documented nutritional & pulmonary care thus providing an excellent subject population for this study. Mentorship under Dr. Dennis Bier, who will provide extensive knowledge regarding the use of stable isotopes, and use of the USDA/ARS Children's Nutrition Research Center will provide an important addition to Dr. Hardin's research training.